Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy.

BACKGROUND: Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery and efficacy for a successful cancer treatment. However, surface functionalization involves complex procedures that increase costs and timelines, presenting challenges for clinical implementation. Biomimetic nanoparticles (BNPs) have emerged as unique drug delivery platforms that overcome the limitations of actively targeted nanoparticles. Nevertheless, BNPs coated with unmodified cells show reduced functionalities such as specific tumor targeting, decreasing the therapeutic efficacy. Those challenges can be overcome by engineering non-patient-derived cells for BNP coating, but these are complex and cost-effective approaches that hinder their wider clinical application. Here we present an immune-driven strategy to improve nanotherapeutic delivery to tumors. Our unique perspective harnesses T-cell exhaustion and tumor immune evasion to develop a groundbreaking new class of BNPs crafted from exhausted T-cells (NExT) of triple-negative breast cancer (TNBC) patients by specific culture methods without sophisticated engineering. METHODS: NExT were generated by coating PLGA (poly(lactic-co-glycolic acid)) nanoparticles with TNBC-derived T-cells exhausted in vitro by acute activation. Physicochemical characterization of NExT was made by dynamic light scattering, electrophoretic light scattering and transmission electron microscopy, and preservation and orientation of immune checkpoint receptors by flow cytometry. The efficacy of chemotherapy-loaded NExT was assessed in TNBC cell lines in vitro. In vivo toxicity was made in CD1 mice. Biodistribution and therapeutic activity of NExT were determined in cell-line- and autologous patient-derived xenografts in immunodeficient mice. RESULTS: We report a cost-effective approach with a good performance that provides NExT naturally endowed with immune checkpoint receptors (PD1, LAG3, TIM3), augmenting specific tumor targeting by engaging cognate ligands, enhancing the therapeutic efficacy of chemotherapy, and disrupting the PD1/PDL1 axis in an immunotherapy-like way. Autologous patient-derived NExT revealed exceptional intratumor accumulation, heightened chemotherapeutic index and efficiency, and targeted the tumor stroma in a PDL1+ patient-derived xenograft model of triple-negative breast cancer. CONCLUSIONS: These advantages underline the potential of autologous patient-derived NExT to revolutionize tailored adoptive cancer nanotherapy and chemoimmunotherapy, which endorses their widespread clinical application of autologous patient-derived NExT.

A Telehealth-Based Cognitive-Adaptive Training (e-OTCAT) to Prevent Cancer and Chemotherapy-Related Cognitive Impairment in Women with Breast Cancer: Protocol for a Randomized Controlled Trial.

BACKGROUND: Many women with breast cancer experience a great number of side effects, such as cognitive impairment, during and after chemotherapy that reduces their quality of life. Currently, research focusing on the use of non-pharmacological, and specifically telehealth interventions to prevent or mitigate them has been insufficient. METHODS: This protocol describes a randomized controlled trial aimed at studying the preventive effects of a videoconferenced cognitive-adaptive training (e-OTCAT) program (ClinicalTrials.gov NCT04783402). A number of 98 eligible participants will be randomized to one of the following groups: (a) the experimental group receiving the e-OTCAT program during 12 consecutive weeks since the beginning of chemotherapy; and (b) the control group receiving and educational handbook and usual care. The primary outcome will be the cognitive function. Secondary measures will be psychological distress, fatigue, sleep disturbance, quality of life and occupational performance. The time-points for these measures will be placed at baseline, after 12 weeks and six months of post-randomization. CONCLUSION: This trial may support the inclusion of multidimensional interventions through a telehealth approach in a worldwide growing population suffering from breast cancer, emphasizing the prevention of cognitive impairment as one of the side effects of cancer and its treatments.

Prevention of Chemotherapy-Induced Peripheral Neuropathy With PRESIONA, a Therapeutic Exercise and Blood Flow Restriction Program: A Randomized Controlled Study Protocol.

OBJECTIVE: This trial will analyze the acute and cumulative effects of a tailored program called PRESIONA that combines therapeutic exercise and blood flow restriction to prevent chemotherapy-induced peripheral neuropathy (CIPN) in individuals with early breast cancer undergoing neoadjuvant chemotherapy. METHODS: PRESIONA will be a physical therapist-led multimodal exercise program that uses blood flow restriction during low-load aerobic and strength exercises. For the acute study, only 1 session will be performed 1 day before the first taxane cycle, in which 72 women will be assessed before intervention and 24 hours post intervention. For the cumulative study, PRESIONA will consist of 24 to 36 sessions for 12 weeks following an undulatory prescription. At least 80 women will be randomized to the experimental group or control group. Feasibility will be quantified based on the participant recruitment to acceptance ratio; dropout, retention, and adherence rates; participant satisfaction; tolerance; and program security. In the efficacy study, the main outcomes will be CIPN symptoms assessed with a participant-reported questionnaire (EORTC QLQ-CIPN20). In addition, to determine the impact on other participant-reported health and sensorimotor and physical outcomes, the proportion of completed scheduled chemotherapy sessions will be examined at baseline (t0), after anthracycline completion (t1), after intervention (t2), and at the 2-month (t3) and 1-year follow-ups (t4). CONCLUSION: The proposed innovative approach of this study could have a far-reaching impact on therapeutic options, and the physical therapist role could be essential in the oncology unit to improve quality of life in individuals with cancer and reduce side effects of cancer and its treatments. IMPACT: Physical therapists in the health care system could be essential to achieve the planned doses of chemotherapy to improve survival and decrease the side effects of individuals with breast cancer. The prevention of CIPN would have an impact on the quality of life in these individuals, and this protocol potentially could provide an action guide that could be implemented in any health care system.

Neurotoxicity prevention with a multimodal program (ATENTO) prior to cancer treatment versus throughout cancer treatment in women newly diagnosed for breast cancer: Protocol for a randomized clinical trial.

A current challenge in breast cancer (BC) patients is how to reduce the side effects of cancer and cancer treatments and prevent a decrease in quality of life (QoL). Neurotoxic side effects, especially from chemotherapy, are present in up to 75% of women with BC, which implies a large impact on QoL. There is a special interest in the preventive possibilities of therapeutic exercise (TE) for these neurological sequelae, and the benefits of TE could be improved when it is combined with vagal activation techniques (VATs). This superiority randomized controlled trial aims to examine the feasibility and efficacy of an 8-week multimodal intervention (ATENTO) based on moderate-vigorous intensity and individualized TE (aerobic and strength exercises) and VAT (myofascial and breathing exercises), on neurotoxicity prevention in women with BC before starting adjuvant chemotherapy (ATENTO-B) versus throughout adjuvant chemotherapy (ATENTO-T). A sample of 56 women newly diagnosed with BC, as calculated with a power of 85%, will be randomly allocated into these two groups. This study could provide an impetus for the introduction of early multimodal intervention methods to prevent neurotoxicity and consequently avoid the QoL deterioration that BC patients presently suffer throughout their treatments.

Angiosarcoma radioinducido de mama. Revisión bibliográfica a propósito de dos casos en nuestro centro / Radiotherapy-related angiosarcoma of the breast. A literature review apropos of two cases treated in our hospital

Objetivo Revisión bibliográfica del diagnóstico y tratamiento actual del angiosarcoma radioinducido de mama. Pacientes Presentamos dos casos de angiosarcoma radioinducido de mama comentándose los aspectos clínicos, diagnósticos y terapéuticos de interés. Conclusión El angiosarcoma de mama radioinducido es un tumor infrecuente que se presenta como complicación tardía en pacientes sometidas a tratamiento conservador del cáncer de mama mediante cirugía y radioterapia. La cirugía es el único tratamiento curativo, aunque su elevada tasa de recaída local requiere de tratamiento multimodal para optimizar los resultados de control local. (AU)

Objective Literature review of the diagnosis and treatment of radiotherapy related angiosarcoma of the breast. Case reportWe present two cases of radiotherapy-related angiosarcoma of the breast treated in our hospital and describe the clinical, diagnostic, and therapeutic features. Conclusion Radiotherapy-related angiosarcoma of the breast is an uncommon tumour that usually presents as a late complication in patients who have undergone surgery and radiotherapy as conservative treatment for breast cancer. Surgery is the only curative treatment. However, because of its high rate of local recurrence, multimodal therapy is required to optimise prevention of recurrence. (AU)

Attenuating Treatment-Related Cardiotoxicity in Women Recently Diagnosed With Breast Cancer via a Tailored Therapeutic Exercise Program: Protocol of the ATOPE Trial.

OBJECTIVE: Therapeutic exercise is already used to ameliorate some of the side effects of cancer treatment. Recent studies examined its preventive potential regarding treatment-related toxicity, which can increase the risk of functional decline and lead to disease recurrence and death. This trial will examine whether the Tailored Therapeutic Exercise and Recovery Strategies (ATOPE) program, performed before treatment, can mitigate the onset and extent of cardiotoxicity beyond that achieved when the program is followed during treatment in recently diagnosed breast cancer patients. METHODS: The intervention has a preparatory phase plus 12 to 18 sessions of tailored, high-intensity exercise, and post-exercise recovery strategies. A total of 120 women recently diagnosed with breast cancer, at risk of cardiotoxicity due to anticancer treatment awaiting surgery followed by chemotherapy and/or radiotherapy, will be randomized to either group. In a feasibility study, measurements related to recruitment rate, satisfaction with the program, adherence to them, the retention of participants, safety, and adverse effects will be explored. In the main trial, the efficacy of these interventions will be examined. The major outcome will be cardiotoxicity, assessed echocardiographically via the left ventricular ejection fraction. Other clinical, physical, and anthropometric outcomes and biological and hormonal variables will also be assessed after diagnosis, after treatment, 1 year after treatment ends, and 3 years after treatment ends. CONCLUSION: Given its potential effect on patient survival, the mitigation of cardiotoxicity is a priority, and physical therapists have an important role in this mitigation. If the ATOPE intervention performed before treatment returns better cardioprotection results, it may be recommendable that patients recently diagnosed follow this program. IMPACT: The ATOPE program will highlight the need for a physical therapist intervention from the moment of diagnosis, in the prevention or mitigation of cardiotoxicity, in women with breast cancer. It could help physical therapists to establish an adequate therapeutic exercise dose adapted to breast cancer patients and to propose correct therapeutic exercise prescription according to the assimilation of the sessions.

Quantity and quality of muscle in patients recently diagnosed with colorectal cancer: a comparison with cancer-free controls.

This cross-sectional study compares the muscle mass, core strength and physical fragility of patients recently diagnosed with colorectal cancer (pRD-CRC) with those of healthy subjects and identifies variables to be considered when designing pre-treatment physical interventions for such patients. Body composition, anthropometric variables, the muscle architecture of the lumbopelvic region, physical fitness and frailty were assessed in 32 pRD-CRC and 29 healthy control subjects. The patients showed a reduction in muscle mass (F = 10.059; P = 0.003), in the width of the lumbar multifidus (F = 21.869; P < 0.001), in the transverse abdominal muscle (U = 323.00; P = 0.042) and in the abdominal strength resistance (F = 12.264; P = 0.001). They were also frailer (P = 0.002) than the controls. These results suggest that pRD-CRC are affected by reduced strength and myopenia, leading to frailty. The early incorporation of these patients into strength-enhancing programs may be advisable.

Enfermedad inflamatoria pélvica: una causa inusual de obstrucción intestinal aguda / Pelvic inflammatory disease: An unusual cause of acute intestinal obstruction

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Uso de trinitrato de glicerilo como tratamiento de hematoma y necrosis del complejo aréola pezón / Nitroglycerin use as treatment of haematoma and necrosis of the nipple-areola complex

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Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study.

BACKGROUND: Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. METHODS: We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. DISCUSSION: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.

Granulomatosis eosinofílica con poliangitis: informe de un caso / Eosinophilic granulomatosis with polyangiitis: A case report

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Relación entre cambios en hemoglobina glucosilada y mejora de la composición corporal en pacientes con obesidad mórbida tras gastrectomía tubular laparoscópica / Relationship between changes in hemoglobin glycosilated and improvement of body composition in patients with morbid obesity after tubular laparoscopic gastrectomy

Introducción y objetivo: El objetivo de nuestro estudio es analizar la posible relación entre los cambios en el perfil glucémico y los parámetros de composición corporal en pacientes con obesidad mórbida tras gastrectomía tubular laparoscópica. Material y métodos: Se realiza un estudio observacional prospectivo de cohortes donde el tamaño muestral es de 69 pacientes. Las variables analizadas son peso corporal, glucemia, hemoglobina glucosilada, lipoprotein high density, lipoprotein low density, triglicéridos y circunferencia cintura y cadera. Para llevar a cabo el objetivo de este estudio se ha utilizado un análisis de la variancia de medidas repetidas (ANOVA) y un posterior análisis de correlación a través del test de Pearson. Resultados: Tras el análisis estadístico se han encontrado una reducción significativa del peso tras la cirugía p < 0,001, una reducción significativa de la hemoglobina glucosilada entre los valores preintervención y a los 6 meses de la cirugía (p<0,036) y un descenso significativo de los perímetros de cintura y cadera (p< 0,001). No existieron diferencias significativas en el resto de variables estudiadas. En el análisis de correlación, se encontró una correlación positiva significativa entre el cambio en concentración de hemoglobina glucosilada y perímetro de cadera (p=0,047; r=0,237), a menor diámetro de cadera, menor concentración de hemoglobina glucosilada. Conclusiones: La gastrectomía tubular laparoscópica se muestra como una técnica efectiva para el tratamiento de pacientes obesos mórbidos con diabetes mellitus tipo 2. La reducción en el perímetro de cadera está relacionada con la reducción de hemoglobina glucosilada a los 6 meses de la intervención

Background and objective: The objective of our study is to analyze the possible relationship between changes in glycemic profile and body composition parameters in morbid obesity patients after tubular laparoscopic gastrectomy. Material and methods: A prospective observational cohort study with 69 patients was performed. The variables analyzed were body weight, blood glucose, hemoglobin, glycosylated, high density lipoprotein, low density lipoprotein, triglycerides, and waist and hip circumference. An analysis of variance of repeated measurements (ANOVA) and a correlation analysis through the Pearson test were carried out. Results: A significant reduction in weight (p<.001 after surgery) and in glycosylated hemoglobin (p<.036) and waist hip (p<.001) were found at 6 months after surgery. There was no significant difference in the rest of the variables studied. In correlation analysis, a significant positive correlation was found between the change in concentration of hemoglobin glycosylated and hip circumference (p=.047; r=0.237), the smaller the hip circumference, the lower the concentration of glycosylated hemoglobin. Conclusions: Tubular laparoscopic gastrectomy is an effective technique for the treatment of morbidly obese patients with type 2 diabetes mellitus. The reduction in the perimeter of hip is related to glycosylated hemoglobin reduction 6 months after intervention

Relationship between changes in hemoglobin glycosilated and improvement of body composition in patients with morbid obesity after tubular laparoscopic gastrectomy. / Relación entre cambios en hemoglobina glucosilada y mejora de la composición corporal en pacientes con obesidad mórbida tras gastrectomía tubular laparoscópica.

BACKGROUND AND OBJECTIVE: The objective of our study is to analyze the possible relationship between changes in glycemic profile and body composition parameters in morbid obesity patients after tubular laparoscopic gastrectomy. MATERIAL AND METHODS: A prospective observational cohort study with 69 patients was performed. The variables analyzed were body weight, blood glucose, hemoglobin, glycosylated, high density lipoprotein, low density lipoprotein, triglycerides, and waist and hip circumference. An analysis of variance of repeated measurements (ANOVA) and a correlation analysis through the Pearson test were carried out. RESULTS: A significant reduction in weight (p<.001 after surgery) and in glycosylated hemoglobin (p<.036) and waist hip (p<.001) were found at 6 months after surgery. There was no significant difference in the rest of the variables studied. In correlation analysis, a significant positive correlation was found between the change in concentration of hemoglobin glycosylated and hip circumference (p=.047; r=0.237), the smaller the hip circumference, the lower the concentration of glycosylated hemoglobin. CONCLUSIONS: Tubular laparoscopic gastrectomy is an effective technique for the treatment of morbidly obese patients with type 2 diabetes mellitus. The reduction in the perimeter of hip is related to glycosylated hemoglobin reduction 6 months after intervention.

Improvements in Health-Related Quality of Life and Pain: A Cohort Study in Obese Patients After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: The principal aim of the study was to investigate the effect of the sleeve gastrectomy (SG) in the quality of life (QoL) and pain in a population of morbidly obese patients. METHODS: Seventy-two SG patients were assessed in this descriptive observational study, before the surgery and 6 months after that. We evaluated health-related QoL (Gastrointestinal Quality of Life Index [GIQLI]) and pain (spontaneous low back pain by Numerical Point Rate Scale [NPRS] and pressure pain thresholds [PPTs]). RESULTS: The results of the analysis of variance (ANOVA) revealed significant improvements in nearly all of the subscales of GIQLI questionnaire after 6 months: gastrointestinal symptoms (P = .01), physical well-being (P < .001), social well-being (P = .03), and total GIQLI score (P < .001), but not for the emotional condition (P = .20). Patients also had improvements in spontaneous low back pain (P = .002), but not in the PPTs in all the body areas explored, including the cervical area, low back, and hands (P > .05). CONCLUSION: Patients receiving SG improved their health-related QoL and low back pain 6 months after the intervention, but this improvement was not so important for pressure pain thresholds in different body areas.

Myofascial Induction Effects on Neck-Shoulder Pain in Breast Cancer Survivors: Randomized, Single-Blind, Placebo-Controlled Crossover Design.

OBJECTIVES: To (1) investigate the immediate effects of myofascial induction (MI), with placebo electrotherapy as a control, on perceived pain, cervical/shoulder range of motion (ROM), and mood state in breast cancer survivors (BCSs) with shoulder/arm morbidity; and (2) examine the relationships between pain modifications and cervical/shoulder ROM on the side affected by breast cancer. DESIGN: Randomized, single-blind, placebo-controlled crossover study. SETTING: Physical therapy laboratory. PARTICIPANTS: BCSs (N=21) who had a diagnosis of stage I-IIIA breast cancer and had completed adjuvant therapy (except hormonal treatment). INTERVENTION: During each session, the BCSs received either an MI (fascial unwinding) intervention focused on the upper limb area following the Pilat approach or placebo pulsed shortwave therapy (control group). Each session lasted 30 minutes, and an adequate washout period of 4 weeks between sessions was established. MAIN OUTCOME MEASURES: The visual analog scale (VAS) for pain and anxiety, shoulder-cervical goniometry for ROM, the Profile of Mood States for psychological distress, and the Attitudes Towards Massage Scale were used. RESULTS: An analysis of covariance (ANCOVA) revealed significant time × group interactions for VAS affected arm (P=.031) but not for VAS cervical (P=.332), VAS nonaffected arm (P=.698), or VAS anxiety (P=.266). The ANCOVA also revealed significant interactions for affected shoulder flexion (P<.001), abduction (P<.001), external rotation (P=.004), and internal rotation (P=.001). Significant interactions for affected cervical rotation (P=.022) and affected cervical lateral flexion (P=.038) were also found. A significant negative correlation was found between changes in VAS affected arm and shoulder/arm internal rotation ROM (r=-.46; P=.03). CONCLUSIONS: A single MI session decreases pain intensity and improves neck-shoulder ROM to a greater degree than placebo electrotherapy for BCSs experiencing pain.

Health-Related Fitness Improvements in Morbid Obese Patients After Laparoscopic Sleeve Gastrectomy: a Cohort Study.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) has demonstrated high long-term effectiveness and major advantages over other techniques. The objective of this study was to analyze changes in physical fitness parameters in morbidly obese patients during 6 months after LSG. METHODOLOGY: We conducted a descriptive observational study with 6-month follow-up in 72 LSG patients, evaluating changes in body mass index (BMI), functional capacity (6-min walking test), hand grip strength (manual dynamometry), flexibility (fingertip-to-floor test), balance (Flamingo test), physical activity level (International Physical Activity Questionnaire, IPAQ), and perception of general physical fitness (International Fitness Scale [IFIS] questionnaire). RESULTS: The ANOVA revealed significant improvements in BMI, functional capacity, flexibility, balance, and physical activity level (P < 0.001) at 6 months, with an improvement in the perception of physical fitness in most cases. No significant changes were found in dominant hand (P = 0.676) or non-dominant hand (P = 0.222) dynamometry. General physical fitness was positively correlated with BMI and distance in the 6-min test, and was negatively correlated with fingertip-to-floor distance. CONCLUSION: Morbidly obese patients showed major improvements at 6 months after LSG in functional capacity, balance, mobility, and physical activity, with no change in grip strength. These improvements were related to a better self-perception of general physical fitness.